Case Of Adenovirus Infection Research Articles

A rare case of adenovirus infection in post renal transplant patient

Human adenovirus is a linear, non-enveloped, double-stranded DNA virus that can cause opportunistic infections. Typically, adenovirus infections result in self-limiting respiratory, gastrointestinal or ocular infections. However, it can cause severe disseminated disease in immunocompromised patients, especially in post-transplant recipients. In kidney transplant recipients, adenovirus infections have an incidence of up to 4.1%, usually manifested as hemorrhagic cystitis and tubulointerstitial nephritis, in the first three months post-transplant. Renal biopsy shows necrotizing granulomatous interstitial nephritis and other features consistent with the viral infection. Investigations like immunohistochemistry and polymerase chain reaction (PCR) help in confirmation of the diagnosis. Resolution of the disease with the reduction in immunotherapy alone supports the role of immunosuppression as a risk factor for adenovirus infection.

Two Novel Adenoviruses in Free-Living British lizards.

In this study, we describe two novel adenoviruses isolated from (i) a common lizard (Zootoca vivipara) found dead and examined post-mortem and (ii) pooled samples from free-living sand lizards (Lacerta agilis agilis). Sequencing indicated the two were closely related atadenovirus strains which were distinct from previously recorded adenoviruses in lizards. Adenoviruses are not always associated with disease in squamates, but morbidity and mortality have been reported. These are the first known cases of adenovirus infection in free-living native British lizards, and further monitoring will be necessary to elucidate the implications of these possible pathogens for vulnerable populations of native reptiles.

Phylogenetic analyses of novel squamate adenovirus sequences in wild-caught Anolis lizards.

Adenovirus infection has emerged as a serious threat to the health of captive snakes and lizards (i.e., squamates), but we know relatively little about this virus' range of possible hosts, pathogenicity, modes of transmission, and sources from nature. We report the first case of adenovirus infection in the Iguanidae, a diverse family of lizards that is widely-studied and popular in captivity. We report adenovirus infections from two closely-related species of Anolis lizards (anoles) that were recently imported from wild populations in the Dominican Republic to a laboratory colony in the United States. We investigate the evolution of adenoviruses in anoles and other squamates using phylogenetic analyses of adenovirus polymerase gene sequences sampled from Anolis and a range of other vertebrate taxa. These phylogenetic analyses reveal that (1) the sequences detected from each species of Anolis are novel, and (2) adenoviruses are not necessarily host-specific and do not always follow a co-speciation model under which host and virus phylogenies are perfectly concordant. Together with the fact that the Anolis adenovirus sequences reported in our study were detected in animals that became ill and subsequently died shortly after importation while exhibiting clinical signs consistent with acute adenovirus infection, our discoveries suggest the need for renewed attention to biosecurity measures intended to prevent the spread of adenovirus both within and among species of snakes and lizards housed in captivity.

Alemtuzumab Used with Fludarabine and Cyclophosphamide (FCC) for Stem Cell Transplantation in Acquired Aplastic Anemia Is Associated with a Low Risk of Graft Versus Host Disease and Viral Infections and with Sustained Engraftment.

Abstract 1084Poster Board I-106Graft rejection and chronic GVHD remain major obstacles to successful outcome after stem cell transplantation (SCT) for aplastic anemia (AA). Using cyclophosphamide (CY) 200mg/kg with ATG, rejection occurs in 5-10% and chronic GVHD in 30-40% of patients transplanted from HLA matched sibling donors (MSD). For unrelated donor (UD) SCT using Fludarabine with CY and ATG, rejection occurs in 18% (30% for patients > 14 years of age) and chronic GVHD in 27%. We have pioneered the use of Alemtuzumab with CY in AA SCT and shown a reduction in GVHD although graft rejection was high at 24%. More recently, Fludarabine has been added to the conditioning to reduce graft rejection. In this retrospective, multi-center study, we report outcomes after SCT for acquired AA in 37 patients using Alemtuzumab, Fludarabine and CY (FCC) conditioning regimen. Alemtuzumab dose was 0.2mg/kg x5 days (n=20), 60mgx1 (n=12), 25mgx4 (n=4) and 40mgx1+30mgx2 (n=1). All patients received Fludarabine 30mg/m2x4 and CY 300mg/m2 x4 (FCC). Patients were transplanted from 1999 to 2009. Median follow up of survivors was 641days (range 72-3547). Disease severity was ‘very severe' in10, ‘severe' in 20 and ‘non-severe' in 7 patients. SCT was performed using MSD in 15 patients (40%) and UD in 22 (60%), of whom all but one were matched for 8/8 or 10/10 alleles. Median age was 35 years (range 8-55). Stem cell source was bone marrow (BM) in 21 (57%), peripheral blood stem cells (PBSC) in 7 (19%), BM+PBSC in 5 (13%) and G-mobilised BM in 4 (11%). Time from diagnosis to SCT was < 12 months in 57% of patients and > 12 months in 41%. 8/15 (53%) of sibling transplants and 18/22 (82%) of UD transplants received immunosuppressive therapy prior to SCT. There were 5 cases of graft failure, early rejection in 2 UD SCT and late graft rejection in 3 (one UD and two MSD). Of the 5 patients with graft rejection, BM was used as the stem cell source in 3, G-mobilised BM in one and PBSC in one. Cumulative incidence of graft failure at 1 year was 15% ± 4% (14% for MSD and 15% for UD SCT). For patients transplanted > 12 months from diagnosis, graft failure was 25% compared with 10% for patients transplanted within 12 months (p= 0.191). Acute GVHD occurred in 13.5% patients, grade I-II in all cases. Chronic GVHD occurred in only one patient (2.7%, extensive). Data for CMV and adenovirus infections was available in 21 patients, and in 20 patients for EBV. CMV reactivation occurred in 2/21 (9.5%) patients, with one case of CMV disease. EBV infection occurred in 2/20 patients (10%): one responded to Rituximab and one patient died from progressive EBV PTLD. There were no cases of adenovirus infection. Overall survival (OS) at 3 years was 89% (93% for MSD and 85% for UD SCT, p= 0.658). For all patients, OS was 95% when time from diagnosis to SCT was < 12 months and 80% for > 12 months (p= 0.273). For patients > 40 years of age, there was no significant difference in OS compared with patients < 40 years old (93% vs 82%). There were 3 deaths, one from chronic GVHD and CMV at day + 427, one from graft failure at day +134 and one due to EBV PTLD at day +180. We conclude that the use of Alemtuzumab with Fludarabine and CY (FCC) for MSD and UD SCT for acquired AA is associated with excellent survival, a low incidence of acute and chronic GVHD and a low incidence of viral infections. DisclosuresMarsh:Genzyme: Consultancy, Honoraria. Off Label Use: Alemtuzumab used for conditioning for stem cell transplantation for aplastic anemia. Gupta:Genzyme: Honoraria, Research Funding.

Life-threatening adenovirus infection in a kidney transplant recipient.

Adenovirus causes 5–10% of all childhood febrile illnesses [1]. In the immunocompetent host, infection is usually associated with mild, self-limiting upper respiratory tract syndromes. Most individuals have serologic evidence of prior adenoviral infection by age 10 [1]. Following initial infection, adenovirus establishes lifelong latent infection in lympho-epithelial tissues [2]. In immunocompromised hosts, the spectrum of adenovirus infection can range from asymptomatic shedding to fatal disseminated disease [2]. It may represent primary infection, usually the case in paediatric transplant recipients, or reactivation of latent disease. Latent viruses may be of donor or recipient origin [2]. Adenovirus infection has been documented in solid organ transplantation, but is relatively rare and therefore a paucity of epidemiologic data exists. This case of adenovirus infection in a kidney transplant recipient is unusual for the severity of allograft dysfunction and the life-threatening nature of disease. It highlights the need for consideration of adenovirus as a cause of fever of unknown origin in the post-transplant setting. Potential therapeutic options are discussed, including use of cidofovir in a dialysis-dependent patient.